Effect of pravastatin on endothelial dysfunction in children with medium to giant coronary aneurysms due to Kawasaki disease.

Abstract

Ongoing low-grade inflammation and endothelial dysfunction persist in children with coronary lesions diagnosed with Kawasaki disease (KD). Statins, frequently used in the management of high cholesterol, have also shown to improve surrogate markers of inflammation and endothelial dysfunction. This study was undertaken to investigate the efficacy and safety of pravastatin in children with coronary artery aneurysms due to KD. The study enrolled 14 healthy children and 13 male children, aged 2-10 years, with medium-to-giant coronary aneurysms for at least 12 months after the onset of KD. Pravastatin was given orally to the KD group at a dose of 5 mg/day for children under 5 and 10 mg/day for children older than 5 years. To determine the effects of pravastatin on endothelial function, high-frequency ultrasound was performed before the start of the study and 6 months after pravastatin therapy. The parameters measured were brachial artery flow-mediated dilation (FMD), non-flow mediated dilation (NMD), and carotid artery stiffness index (SI). High sensitive C-reactive protein (hs-CRP) levels, the circulating endothelial progenitor cells (EPCs) number, and serum lipid profiles were also determined at baseline and after 6 months of pravastatin treatment. Before treatment, the KD group had significantly decreased FMD (P<0.05) and increased SI and hs-CRP levels (P<0.05) compared with controls. After 6 months of pravastatin therapy, FMD improved significantly compared to the baseline KD group (3.16±6.49 to 10.05±7.74, P<0.05), but remained significantly less than that in the control group with no significant changes in NMD and SI. There were significant decreases in markers of inflammation after treatment. The hs-CRP levels decreased significantly from 2.93±0.81 mmol/L to 2.14±0.82 mmol/L (P<0.05) and the serum apo-B and apo-B/apo-A1 ratio were also reduced (P<0.05) in the KD group. However, the circulating EPC number was not significantly different between baseline and that following pravastatin treatment in the KD group and the control group (P>0.05). No significant complications were noted with paravastatin therapy. Pravastatin improves endothelial function and reduces low-grade chronic inflammation in patients with coronary aneurysms due to KD. Children with coronary aneurysms due to KD may benefit from statin therapy.